Outcomes to first-line pembrolizumab in patients with PD-L1-high (≥50%) non–small cell lung cancer and a poor performance status

Abstract

BackgroundPatients with non–small cell lung cancer (NSCLC) and a poor Eastern Cooperative Oncology Group Performance Status (ECOG PS) have been excluded from phase III immunotherapy clinical trials. We sought to evaluate clinical outcomes to first-line pembrolizumab in patients with advanced NSCLC, a PD-L1 Tumor Proportion Score (TPS) of ≥50%, and an ECOG PS of 2.MethodsWe performed a multicenter retrospective analysis of patients with metastatic NSCLC and a PD-L1 TPS of ≥50% (negative for genomic alterations in EGFR and ALK) who received treatment with first-line pembrolizumab. Clinical outcomes were compared in patients based on ECOG PS.ResultsAmong the 234 patients, 83.3% (n=195) had an ECOG PS of 0 or 1, and 16.7% (n=39) had an ECOG PS of 2. The baseline clinicopathological characteristics were balanced between the ECOG PS 0–1 vs 2 groups in terms of age, sex, tobacco use, histology, KRAS mutation status, presence of other potentially targetable driver mutations (BRAF, MET, HER2, RET), presence of brain metastases, and PD-L1 TPS distribution. Compared with patients with an ECOG PS of 0 or 1, patients with an ECOG PS of 2 had a significantly lower objective response rate (43.1% vs 25.6%; p=0.04), a numerically shorter median progression-free survival (6.6 months vs 4.0 months; HR 0.70 (95% CI 0.47 to 1.06); p=0.09), and a significantly shorter median overall survival (20.3 months vs 7.4 months; HR 0.42 (95% CI 0.26 to 0.68); p<0.001). On disease progression, patients with an ECOG PS of 2 were significantly less likely to receive second-line systemic therapy compared with patients with an ECOG PS of 0–1 (65% vs 22.2%, p=0.001).ConclusionsA subset of patients with NSCLC and an ECOG PS of 2 can respond to first-line pembrolizumab. However, clinical outcomes in this population are often poor and use of second-line systemic therapy is infrequent.

Association of Performance Status With Survival in Patients With Advanced Non–Small Cell Lung Cancer Treated With Pembrolizumab Monotherapy

“…Subgroup analyses in patients with an ECOG PS score at least 2 and tumor PD-L1 TPS of at least 50%, any tumor PD-L1 TPS treated with pembrolizumab in the first-line setting, and tumor PD-L1 TPS of at least 50% who were treated with pembrolizumab in the first-line setting showed results consistent with prior studies, with the major exception of shorter OS in our cohort compared with the Pembrolizumab in Patients With Non–Small Cell Lung Cancer of Performance Status 2 (PePS2) trial 7 , 14 , 15 , 16 , 17 (eTable 3 in the Supplement ). Further analysis of patients belonging to the group with ECOG PS scores of at least 2 who achieved vs did not achieve durable clinical benefit (defined as PFS >6 months) revealed no differences in baseline clinicopathological characteristics (eTable 4 in the Supplement ); however, those with durable clinical benefit had a higher likelihood of developing any grade immune-related adverse events than those without durable clinical benefit (5 [71.4%] vs 4 [18.2%]; P = .02).…”

“…Other retrospective studies have focused on a further selected subgroup of patients with advanced NSCLC with PD-L1 TPS of at least 50% and ECOG PS scores of 2 treated with first-line pembrolizumab monotherapy. 14 , 15 , 16 Results from the subgroup analysis in our cohort mirror the results reported from the largest study of such patients, 14 which reported a median PFS and OS of 2.4 months and 3.0 months, respectively (eTable 3 in the Supplement ).…”

Real-world outcomes of immunotherapy–based regimens in first-line advanced non-small cell lung cancer

“…These results highlight differences between patients in clinical practice and those in clinical trials, which are limited to providing information from select and relatively well-performing patients. Regardless of treatment regimen, patients with ECOG PS >1 had shorter median OS, which was reported previously from studies of 1L I-O monotherapy in patients ≥50 % tumor PD-L1 expression [28][29][30]. Older age was associated with shorter median OS regardless of treatment regimen in patients with non-squamous NSCLC but not in those with squamous histology.…”

Nationwide Survival Benefit after Implementation of First-Line Immunotherapy for Patients with Advanced NSCLC—Real World Efficacy

“…In addition, patients with brain metastases have an mOS comparable to that of patients without brain metastases [ 13 , 14 ]. By contrast, PS ≥ 2 has been associated with significantly reduced mOS, independent of treatment line, and a systematic review demonstrated a pooled mOS hazard ratio (HR) of 2.72 compared to PS 0–1 [ 15 , 16 ]. RWS indicate significantly reduced response rates and impaired mOS in patients with bone metastases (BoM) compared to those without [ 17 , 18 ].…”